Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERPI-1Cat.No.:HY-101246CASNo.:269730-03-2分?式:C??H??NO?分?量:297.31作?靶點(diǎn):RET作?通路:ProteinTyrosineKinase/RTK儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:125mg/mL(420.44mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.3635mL16.8175mL33.6349mL5mM0.6727mL3.3635mL6.7270mL10mM0.3363mL1.6817mL3.3635mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請?jiān)?個?內(nèi)使?，-20°C儲存時，請?jiān)?個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(7.00mM);Suspendedsolution;Needultrasonic1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性RPI-1?種特異的?服2-吲哚啉酮Ret酪氨酸激酶抑制劑。RPI-1抑制?甲狀腺髓樣癌TT細(xì)胞增殖、Ret酪氨酸磷酸化、Ret蛋?表達(dá)及PLCgamma、ERKs和AKT的活化。具有抗腫瘤活性。體外研究TPC-1cellsaresensitivetothegrowthinhibitoryeffectofRPI-1withanIC50of5.1μM,following72hoursoftreatment.RPI-1(7.5-60μM)inhibitsRet/Ptc1autophosphorylationinTPC-1cells.RPI-1inhibitoryeffectsintheTPC-1cellcultureconditionsleadtoinhibitionofpathwaysinvolvingJNK2andAKT[1].TheRPI-1IC50valueforcellproliferationis3.6μMinNIH3T3cellsexpressingtheRetmutantcomparedwith16μMinnon-transfectedNIH3T3cells,andthatforcolonyformationinsoftagarwas2.4μMand26μMinRETmutant-transfectedandH-RAS-transfectedNIH3T3cells,respectively.InNIH3T3cellsexpressingtheRetmutant,Retproteinandtyrosinephosphorylationwereundetectableafter24hoursofRPI-1treatment.InTTcells,RPI-1inhibitsproliferation,Rettyrosinephosphorylation,Retproteinexpression,andtheactivationofPLCgamma,ERKsandAKT[2].體內(nèi)研究RPI-1(50,100mg/kg;p.o.;twiceadayfor10days)inhibitsthetumorgrowthofTTxenograftsby81%[2].AnimalModel:8-to11-week-oldfemaleathymicnudeCD-1mice(bearingTTcells)[2]Dosage:50,100mg/kgAdministration:P.o.;twiceadayfor10daysResult:Adose-dependenteffectontumorgrowthwasobserved,withadoseof2*50mg/kg/dayresultinginlesstumorweightinhibitionthanthe2*100mg/kg/daydoseafter10daysoftreatment.REFERENCES[1].LanziC,etal.InactivationofRet/Ptc1oncoproteinandinhibitionofpapillarythyroidcarcinomacellproliferationbyindolinoneRPI-1.CellMolLifeSci.2003;60(7):1449-1459.[2].CuccuruG,etal.CellulareffectsandantitumoractivityofRETinhibitorRPI-1onMEN2A-associatedmedullarythyroidcarcinoma.JNatlCancerInst.2004;96(13):1006-1014.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedical